The present invention relates generally to the field of medical devices suitable for in vivo use, such as implantable devices, indwelling devices, catheters and delivery systems. More particularly, the present invention relates to implantable medical devices, such as endoluminal stents, that are capable of acting as sensors and/or actuators in vivo.
With the advent of microelectromechanical system (MEMs) technology, manufacture of very small scale devices has become feasible. The principal application of MEMs technology has, heretofore, been in the electromechanical arts, in particular fluidics and fluid sensors. The present invention, however, adapts MEMs technology to the field of medical devices and, in particular, to the field of implantable medical devices that are designed to sense in vivo conditions, alter the geometry of the device, and/or deliver metered doses of bioactive substances in vivo.
The field of implantable MEMs based medical devices has extended to diagnostic microsystems, including miniature mass spectrometers, molecular-recognition biosensors, and microfluidic processors, surgical Microsystems, such as microsensors and micromotors, and therapeutic Microsystems, such as implantable and transdermal drug delivery Microsystems. Such types of microdevices are described in Polla, D. L., et al., “Microdevices in Medicine,” Ann. Rev. Biomed. Eng. 2000, 02:551–576, which is hereby incorporated by reference. Further description of implantable medical sensors is found in U.S. Pat. No. 6,201,980, which is hereby incorporated by reference. Further description of a microactuator for controlled drug delivery may be found at Low, L. M., et al., “Microactuators toward microvalves for responsive controlled drug delivery,” Sensors and Actuator, B 678 (2000) 149–160, which is also hereby incorporated by reference.
Micropumps, high resolution microaccelerometers, and electrostatic linear motors are examples of micro-scale electromechanical machines that rely upon low-voltage and low power consumption requirements. See, e.g., Yun, K. S., et al., “A Surface-Tension Driven Micropump for Low-voltage and Low-Power Operations,” J. Microelectromechanical Sys., 11:5, October 2002, 454–461, Yeh, R., et al., “Single Mask, Large Force, and Large Displacement Electrostatic Linear Inchworm Motors,” J. Microelectromechanical Sys., 11:4, August 2002, 330–336, and Loh, N. C., et al., “Sub-10 cm3 Interferometric Accelerometer with Nano-g Resolution,” J. Microelectromechanical Sys., 11:3, June 2002, 182–187, each of which is hereby incorporated by reference.
Conducting polymers have been used as sensors for the development of electronic tongues by fabricating nanostructured films for use as individual sensing units. The films operate by impedance spectroscopy for signal transduction in the frequency range of 1–1 MHz to detect trace amounts of tastants and inorganic contaminants in liquid systems. Riul, Jr., A., et al., “An Artificial Taste Sensor Based On Conducting Polymers,” Biosensors and Bioelectronics, 00 (2003) 1–5, which is hereby incorporated by reference. In a related vein, hydrogels and conducting polymers have been combined as an electroactive hydrogel composite that traps enzymes within the composite matrix for biosensor construction and chemically stimulated controlled release. Glucose, cholesterol and glactose amperometric biosensors have been made using this composite material that display extended linear response ranges between 10−5 to 10−2 M with response times of less than sixty seconds. pH sensors were made by cross-linking the hydrogel component with dimethylaminoethyl methacrylate monomer. See, Brahim, S., et al., “Bio-smart Hydrogels: Co-joined Molecular Recognition and Signal Transduction in Biosensor Fabrication and Drug Delivery,” Biosensors and Bioelectronics, 17 (2003) 973–981, which is hereby incorporated by reference.
Single crystalline MgO nanotubes filed with Gallium have been used as wide-temperature range nanothermometers. See, e.g., Li, Y. B., et al. “Ga-filled Single-Crystalline MgO Nanotube: Wide-temperature Range Nanothermometer,” App. Phys. Let., 83:5, August 2003, 999–1001, which is hereby incorporated by reference.
It has been recognized that ion-channel switches may be used in biosensors and the current flux generated by ion's passing through the ion channel may serve as a basis for sensing a given condition. For example, an ion-channel switch has been made of a lipid membrane containing gramicidin ion channels linked to antibodies and tethered to a gold electrode. This tethered membrane creates an ionic reservoir between the gold electrode and the membrane which is electrically accessed through connection to the gold electrode. In the presence of an applied potential, ions flow between the reservoir and the external solution when the channels are conductive. When the ion current is switched off, mobile channels diffusing within the outer half of the membrane become crosslinked to the antibodies and immobilized. See, Cornell, B. A., et al., “A Biosensor that uses Ion-channel Switches,” Letters to Nature, 1997.
Finally, it is now known that electrical fields effect endothelial cell migration. See, Li, X., et al., “Effects of Direct Current Electric Fields on Cell Migration and Actin Filament Distribution in Bovine Vascular Endothelial Cells,” J. Vasc. Res., 2002; 39:391–404, which is hereby incorporated by reference. Controlling endothelial cell migration is a significant step toward designing implantable devices that exhibit greater healing responses. Thus, by designing implantable devices that employ controlled electrical fields, endothelial cells will be more susceptible to binding to the device and propagating along the device surfaces to promote rapid and complete healing and minimize smooth muscle cell proliferation or thrombogenic effects.
In order to design implantable devices having controlled electrical fields, advantageous use may be made of interdigitated electrodes to create a galvanotactic medical device. Interdigitated electrodes have been employed in dielectrophoresis to separate live and heat-treated Listeria innocua cells on microfabricated devices employing interdigitated electrodes by utilizing the difference in dielectric properties between the alive and dead cells, Li, H., et al., at http://www.nnf.cornell.edu/2002cnfra/2002cnfra54.pdf and Li, H., “Dielectrophoretic Separation and Manipulation of Live and Heat-Treated Cells of Listeria on Microfabricated Devices with Interdigitated Electrodes,” J. Sensors and Actuators, Apr. 2002 which are hereby incorporated by reference. Interdigitated microsensor electrodes, also called interdigitated arrays are microfabricated from patterns of noble metals deposited on an insulating substrate chip. These devices are designed for simultaneous interrogation of electrical, electrochemical or optical properties of polymeric films and coatings in microelectrochemistry and electrical/electrochemical impedance spectroscopy. See, e.g., Guiseppi-Elie, A., “Measuring Electrical Materials Properties Using Microfabricated Interdigitated microsensor Electrodes (IMEs) and Independently Addressable Microband Electrodes (IAMEs),” An ABTECH Application Note, http://www.abtechsci.com/pdfs/resist0501.pdf, May 2001, which is hereby incorporated by reference.